Use of glucosamine and glucosamine derivatives for quick alleviation of itching or localized pain

ABSTRACT

The present invention relates to the new use of glucosamine and/or its derivatives for the preparation of a therapeutical composition for treating and quick relief of itching and/or local pain which results from a variety of causes. The invention further relates to therapeutical compositions for use in this treatment.

This application is a 371 of PCT/EP98/03175 filed May 22, 1998.

FIELD OF INVENTION

The invention relates to the preparation of a topical medication forvery quick alleviation and relief of itching and/or localized paincaused by a wide range of medical indications.

BACKGROUND OF THE INVENTION

Itching (pruritus) has a lot of underlying causes and can lead to a lotof complications by scratching. Itching may be associated with localpain. Pain can also occur independently. Both local pain and itchingcomprise the sensation associated with a lot of causes: inflammation,dry skin, infection by micro-organisms such as bacteria, fungi andviruses, corns, wounds, ulcers, stings, insect bites, allergicreactions, hyper proliferation of the epithelial layer, different typesof treatment with chemicals, affecting the skin, eczema, etc. But thereis also local pain associated with other affections, such as tendinitis,rheumatism and rheumatic affections, such as reumatalgia, reumatidereumatismus articulorum acutus, reumatismus articulorum chronicus,reumatismus musculorum, reumatismus nervosum, reumatismus nodosum,rheumatoid affections, different kinds of arthritis such as arthritisurica, arthritis acuta, arthritis sicca, arthritis hyperthrophica,arthritis infectiosa, arthritis rheumatica, different forms ofarthrosis, skin burning by sun, other irradiations, chemicals or heatsources.

In all these and other cases pain and/or itching may very often bedifficult to treat. Moreover, oral pain killers may have undesired sideeffects due to their systemic mode of action, especially when taken overa prolonged period of time. Itching in itself can be very inconvenientand scratching can deteriorate the condition.

It is therefore desirable and thus the object of the invention toprovide a means for topically treating itching and local pain.

This object was achieved according to the invention when it was foundthat glucosamine and derivatives thereof when applied topically arecapable of controlling, reducing and also inhibiting the initiation ofitching and pain caused by a whole range of unrelated conditions.

The medicinal capacity of glucosamine after oral ingestion thereof in alimited number of diseases has been described in the literature. A pilotstudy of the oral use of N-acetyl-D-glucosamine as a potential treatmentfor patients with osteoarthritis was published by Talent & Gracy (1996).The potential use of oral glucosamine for wound healing and treatmentfor osteoarthritis is discussed by McCarty (1994 and 1996). The use ofglucosamine in non-specific inflammatory bowel diseases is documented byAasakura et al. (1995). Reichelt et al. (1994) demonstrated the efficacyand safety of intramuscular glucosamine sulfate in osteoarthritis of theknee.

The use of glucosamine as non steroidal anti-inflammatory drug inreducing the signs and symptoms of osteoarthritis and rheumatoidarthritis is documented by Spencer-Green (1993) and Setnikar (1992). Thetoxicity of glucosamine for tissue culture cells and the antiviralactivity of glucosamine depending on the cell-type and cell-line weredemonstrated by Schmidt et al. (1989) and Delgadillo & Vanden Berghe(1988).

More complicated glucosamine compounds were evaluated for use inpatients with osteoarthritis of the knee. In the study by Dragani et al.(1989, 1990) heparin-glucoronil glucosaminoglycan was used in along-term study for 30 days in a 3 daily administration of the drug.

All of these prior art documents are however concerned with oral intakeof glucosamine or a derivative thereof. Based on this systemic mode ofaction it could not be expected that topical application of the compoundand/or its derivative(s) could have an alleviating effect on itching andpain.

SUMMARY OF THE INVENTION

The present invention provides for the use of glucosamine and/or itsderivatives for the preparation of a therapeutical composition for thetopical treatment of itching and/or pain. The effect of the mediation isan acupuncture-like effect, i.e. resulting in a very quick painreduction.

The invention thus provides topical medicaments for the alleviation ofitching and pain. It has surprisingly been found that this alleviationcan already take place in a very short delay of time (<1 minute) bysingle topical treatment. The use of glucosamine or glucosaminederivatives for the topical treatment of indications involving painand/or itching were never described before. It is also totally new andunexpected that water-soluble compounds, such as glucosamine orglucosamine derivatives, are at all able to penetrate the skin or mucosaand act so quickly on neurons and nerve impulses causing the sensationof irritation and pain. The effect is therefore called: anacupuncture-like effect.

DISCLOSURE OF THE INVENTION

The use according to the present invention requires glucosamine and/orone or more monomeric glucosamine derivatives such as:

D-glucosamine hydrochloride

D-glucosamine sulfate

D-glucosamine iodide or other salts of D-glucosamine

N-acetyl D-glucosamine and their salts

Chitin hydrolysate

Chitosane hydrolysate

Glucosamine phosphates, sulfates, or acetates and their salts

D-glucosaminic acid

N-acetyl D-glucosamine phosphates, sulfates and their salts

Hydrolysates of chitin and chitosane can be obtained by chitinase.

The compounds mentioned here are preferably comprised in thetherapeutical compositions (also referred to herein as “topicalmedicament”) of the invention in a concentration from 0.1% to 15% (w/w),most preferably from 1% to 10% (w/w).

Topical medicaments prepared according to the invention may furthercomprise other active compounds for healing diseases that areaccompanied by local itching or pain, such as disinfectants,antibiotics, antifungal compounds, wound healing compounds, cosmeticcompounds improving the skin conditions, anti-inflammatory compounds,anti-allergic compounds, anti-rheumatic compounds, anti-arthriticcompounds, other pain or itching relieving compounds, etc.

According to the invention it has been found that the itching or localpain is completely removed or significantly reduced in a short delay oftime of even less than 1 minute for a significant period of at leastmore than 1 hour considered that appropriate concentrations of the drugare used. Appropriate concentrations comprise more than about 0.1% (w/w)glucosamine compound per gram cream, gel, ointment, solution, etc..

All topical medicaments, prepared according to the invention, may beprepared in any conventional form or in other forms suitable for topicaluse on the skin or mucous membranes. These forms also include all formswith sustained release compositions or pre-dispersed plasters and otherforms containing an acceptable carrier for the compounds.

Cosmetic acceptable carriers and additives may include: forms ofvaseline, oils, emollients, surfactants, humefactants, powders, water,preservatives, agents increasing the viscosity such as polysaccharides,polypeptides, fragrances, anti-foam agents, opacifiers, colorants, eachin their amount to accomplish their typical function. The basiccompositions of the various topical application forms described here arewell within the reach of the skilled person.

The present invention will be further illustrated in the followingexamples, which are in no way intended to be limiting to the invention.

EXAMPLES

Formulation

Glucosamine or one or more of its derivatives was added in theappropriate amount to one of the following formulations. Thecompositions thus obtained were tested as described in the Examples. Allpercentages are by weight (w/w) unless otherwise indicated.

Formulation 1

Water

Formulation 2 Cutina MD ™ 4% (Henkel, Germany) Lanette N ™ 3% (Henkel,Germany) Isopropylmyristate 3% (Henkel, Germany) Oleum Amygdalae 4% Ph.Eu II (Conforma, Belgium) Glycerol 5% Ph. EU II (Conforma, Belgium)Methylparahydroxybenzoate 0.2% Propylparahydroxybenzoate 0.02% Aquadestillata ad 100

Formulation 3 Lanette O ™ 8% (Henkel, Germany) Emulgin B2-C1000 ™ 4%(Henkel, Germany) Oleum Amygdalae 5% Ph. Eu II (Conforma, Belgium)Lanette 16 ™ 2% (Henkel, Germany) Glycerol 6% Ph. Eu II (Conforma,Belgium) Methylparahydroxybenzoate 0.2% Propylparahydroxybenzoate 0.02%Aqua destillata ad 100

Example 1

A patient (female; 52 years) suffering from sore throat caused byβ-hemolytic streptococci was treated with a water solution(formulation 1) of N-acetyl-glucosamine (8% w/w). The solution wassprayed into the mouth during 10 seconds in order to treat the infectedarea. Pain relief occurred already 20 seconds after application andlasted for at least 1.5 hour.

12 hours later the same patient was treated with spray containingglucosamine HCl (9% w/w and 20% glycerol and 10% alcohol in water). Painrelief occurred again very quickly, 36 seconds after application andlasted for at least 2 hours.

Example 2

A patient (male; 42 years) suffering from tendinitis caused bypracticing tennis was treated with formulation 2 containing glucosaminesulphate 5% (w/w). The cream was normally applied on the skin during 2minutes to allow the penetration. Pain relief occurred already after 50seconds and lasted for at least 2 hours. After 12 hours the same patientwas treated with formulation 2 without glucosamine. There was no painrelief after similar application.

Example 3

A patient (female; 53 years) suffering from herpes simplex type Iinfection around the nose showing extensive fissures was treated withformulation 3 containing 3% glucosamine sulfate (w/w). Already after 30seconds pain and itching relief occurred and lasted during 3 hours.Remarkably, most of the fissures were closed after 5 hours.

Example 4

A patient (female; 53 years) suffering from pain in the knee caused by alight collision during a car accident was treated with formulation 3containing 10% (w/w) glucosamine sulfate. Pain relief occurred after 50seconds and lasted during 3 hours. After 3 new successive treatmentsevery 4 hours the pain was completely gone.

Example 5

A child (male; 8 months) suffering from diaper allergy was treated withcomposition 2 containing 5% (w/w) glucosamine HCl instead of othercommonly used oils. After applications for 1 week (3 times a day) therewas always immediate relief of itching and pains.

Example 6

A patient (female; 51 years) with a tendinitis due to the practice ofbowling sport was treated 2 days after the onset of pain withcomposition 3 containing 6% (w/w) N-acetyl D-glucosamine. Pain reliefoccurred 25 seconds later. After 5 successive treatments (every 2 hours)pain was completely reduced.

Example 7

A patient with allergy for cats (male; 30 years) was confronted with astroked cat (2 years old) in a closed room (6 m×4 m×3 m) during 10minutes. 8 minutes later itching started all over the forehead andprogressed after 15 minutes to the nose (external x internal).

The patient was treated on the left side of the forehead withcomposition 3 and on the right side of the forehead with composition 3containing 5% (w/w) glucosamine HCl. Itching completely disappearedafter 45 seconds on the right side while there was still itching on theleft side. The nose was also treated inside and outside with the activecream. Itching decreased drastically already after 50 seconds.

Example 8

A patient (male; 17 years) with nettle rash on both hands, 10 minutesafter contact with the nettle plants, was treated with composition 3containing 6% (w/w) glucosamine sulfate on the left hand and composition3 on the right hand.

Two seconds later the itching was drastically reduced on the left handwhile no relief occurred on the right hand.

Example 9

A patient (male; 52 years) suffering from arthritis urica, and nottaking any medication, was treated with composition 2 containing 9%(w/w) glucosamine HCl all over the affected right foot by 4 successivetreatments with an interval of 10 minutes. Gradually strong pain reliefoccurred and lasted for 4 hours.

Example 10

A patient suffering from eczema (atopical) (male; 14 years) on thearm-bends was treated with composition 3 containing 8% (w/w) glucosamineHCl on the left arm and composition 3 on the right arm.

Itching decreased drastically after 15 seconds and lasted during 2 hoursonly on the left arm. From the above it follows that the therapeuticalcompositions of the invention can be used to alleviate itching and painwhich result from a variety of causes. The relief is obtained veryquickly and lasts for a considerable period of time.

REFERENCES

Aasakura, H. et al., Nippon-Naika-Gekki-Zasshi 84(11):1815-20 (1995)

Delgadillo, R. A. & Vanden Berghe, D. A., J. Pharm. Pharmacol 40:488-493(1988)

Dragani, L. et al., Minerva Med. 80(4):397-403 (1989)

Dragani, L. et al., Riv. Fur. Sci. Med. Farmacol. 12:283-295 (1990)

McCarty, M. F., Med. Hypotheses 42(5):323-327 (1994)

McCarty, M. F., Med. Hypotheses 47(4):273-275 (1996)

Reichelt, A. et al., Arzneimittel Forschung 44(1):75-80 (1994)

Schmidt, R. J. et al. J. Pharm. Pharmacol 41:784-784 (1989)

Setnikar, I., Int. J. Tissue-React. 14(5):253-261 (1992)

Spencer-Green, G., Postgrad. Med. 93(7):129-140 (1993)

Talent, J. M. & Gracy, R. W., Clin. Ther. 18(6:1184-1190 (1996)

What is claimed is:
 1. A method for the quick relief of itching and/orpain, comprising applying an effective amount of glucosamine and/or oneor more of its derivatives to the skin of an animal or human in need ofsuch topical treatment, thereby already significantly reducing itchingand/or pain in less than one minute.
 2. The method according to claim 1,wherein said effective amount of glucosamine and/or one or more of itsderivatives is selected from the group consisting of salts ofD-glucosamine, in particular D-glucosamine hydrochloride, D-glucosaminesulfate, D-glucosamine iodide; N-acetyl D-glucosamine and its salts;chitin hydrolysate; chitosane hydrolysate; glucosamine phosphates,sulfates, or acetates and their salts; D-glucosaminic acid; N-acetylD-glucosamine phosphates, sulfates and their salts.
 3. The methodaccording to claim 1 wherein said effective amount of glucosamine isadmixed, prior to its application to the skin, with at least oneadditional therapeutical compound for further treating the medicalcondition associated with said need for topical treatment.
 4. The methodaccording to claim 3 wherein said at least one additional therapeuticalcompound is selected from the group consisting of disinfectants,antibiotics, antifungal compounds, wound healing compounds, cosmeticcompounds improving the skin conditions, anti-inflammatory compounds,anti-allergic compounds, anti-rheumatic compounds, anti-arthriticcompounds, anti-blood coagulant compounds, other pain or itchingrelieving compounds.